K-ras codon-specific mutations produce distinctive metabolic phenotypes in human fibroblasts

Pedro Vizan, Laszlo G. Boros, Agnes Figueras, Gabriel Capella, Ramon Mangues, Sara Bassilian, Shu Lim, Wai Nang P. Lee, Marta Cascante

Research output: Indexed journal article Articlepeer-review

104 Citations (Scopus)


Among K-ras mutations, codon 12 mutations have been identified as those conferring a more aggressive phenotype. This aggressiveness is primarily associated with slow proliferation but greatly increased resistance to apoptosis. Using transfected NIH3T3 fibroblasts with a mutated K ras mini-gene either at codon 12 (K12) or at codon 13 (K13), and taking advantage of [1,2- 13C 2]glucose tracer labeling, we show that codon 12 mutant K-ras (K12)-transformed cells exhibit greatly increased glycolysis with only a slight increase in activity along pathways that produce nucleic acid and lipid synthesis precursors in the oxidative branch of the pentose phosphate pathway and via pyruvate dehydrogenase flux. K13 mutants display a modest increase in anaerobic glycolysis associated with a large increase in oxidative pentose phosphate pathway activity and pyruvate dehydrogenase flux. The distinctive differences in metabolic profiles of K12 and K13 codon mutated cells indicate that a strong correlation exists between the flow of glucose carbons towards either increased anaerobic glycolysis, and resistance to apoptosis (K12), or increased macromolecule synthesis, rapid proliferation, and increased sensitivity to apoptosis.

Original languageEnglish
Pages (from-to)5512-5515
Number of pages4
JournalCancer Research
Issue number13
Publication statusPublished - 1 Jul 2005
Externally publishedYes


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